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Lysosomes are cellular organelles that contain acid hydrolase enzymes that break down waste materials and cellular debris. These are non-specific. They can be described as the stomach of the cell. They are found in animal cells, while their existence in yeasts and plants are disputed. Some biologists say the same roles are performed by lytic vacuoles,[1] while others suggest there is strong evidence that lysosomes are indeed in some plant cells.[2] Lysosomes digest excess or worn-out organelles, food particles, and engulf viruses or bacteria. The membrane around a lysosome allows the digestive enzymes to work at the 4.5 pHthey require. Lysosomes fuse with vacuoles and dispense their enzymes into the vacuoles, digesting their contents. They are created by the addition of hydrolytic enzymes to early endosomes from the Golgi apparatus. The name lysosome derives from the Greek words lysis, to separate, and soma, body. They are frequently nicknamed "suicide-bags" or "suicide-sacs" by cell biologists due to their autolysis. Lysosomes were discovered by the Belgian cytologist Christian de Duve in the 1960s.
The size of a lysosome varies from 0.1–1.2 μm.[3] At pH 4.8, the interior of the lysosomes is acidic compared to the slightly alkaline cytosol (pH 7.2). The lysosome maintains this pH differential by pumping protons (H+ ions) from the cytosol across themembrane via proton pumps and chloride ion channels. The lysosomal membrane protects the cytosol, and therefore the rest of the cell, from the degradative enzymes within the lysosome. The cell is additionally protected from any lysosomal acidhydrolases that drain into the cytosol, as these enzymes are pH-sensitive and do not function well or at all in the alkaline environment of the cytosol.This ensures that cytosolic molecules and organelles are not lysed in case there is leakage of the hydrolytic enzymes from the lysosome.
Lysosomes are the cell's waste disposal system and can digest some compounds. They are used for the digestion ofmacromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material, like foreign invading microbes),endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (where in old or unneeded organelles or proteins, or microbes that have invaded the cytoplasm are delivered to the lysosome). Autophagy may also lead to autophagic cell death, a form of programmed self-destruction, or autolysis, of the cell, which means that the cell is digesting itself.
Other functions include digesting foreign bacteria (or other forms of waste) that invade a cell and helping repair damage to theplasma membrane by serving as a membrane patch, sealing the wound. In the past, lysosomes were thought to kill cells that are no longer wanted, such as those in the tails of tadpoles or in the web from the fingers of a 3- to 6-month-old fetus.
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[edit]Formation
Many components of the animal cell can be seen recycling and sharing their membranous units. For instance, in endocytosis, a portion of the cell’s plasma membrane pinches off to form a vesicle that will eventually fuse with an organelle within the cell. Without active replenishment, the plasma membrane would continuously decrease in size. It is thought that lysosomes participate in this dynamic membrane exchange system and are formed by a gradual maturation process from endosomes.[4]
The production and transport of lysosomal proteins suggest one method of lysosome sustainment. Lysosomal protein genes are transcribed in the nucleus. mRNA transcripts exit the nucleus into the cytosol, where they are translated by ribosomes. The nascent peptide chains are translocated into the rough endoplasmic reticulum, where they are modified. Upon exiting the endoplasmic reticulum and entering the Golgi apparatus via vesicular transport, a specific lysosomal tag, mannose 6-phosphate, is added to the peptides. The presence of these tags allow for binding to mannose 6-phosphate receptors in the golgi apparatus, a phenomenon that is crucial for proper packaging into vesicles destined for the lysosomal system.[5]
Upon leaving the golgi apparatus, the lysosomal enzyme-filled vesicle fuses with a late endosome, a relatively acidic organelle with an approximate pH of 5.5.[5] This acidic environment causes dissociation of the lysosomal enzymes from the mannose 6-phosphate receptors[5]. The enzymes are packed into vesicles for further transport to established lysosomes.[5] The late endosome itself can eventually mature into a mature lysosomes, as evidenced by the transport of endosomal membrane components from the lysosomes back to the endosomes.[4]
[edit]Lysosomotropism
Weak bases with lipophilic properties accumulate in acidic intracellular compartments like lysosomes. While the plasma and lysosomal membranes are permeable for neutral and uncharged species of weak bases, the charged protonated species of weak bases do not permeate biomembranes and accumulate within lysosomes. The concentration within lysosomes may reach levels 100 to 1000 fold higher than extracellular concentrations. This phenomenon is called "lysosomotropism"[6] or "acid trapping". The amount of accumulation of lysosomotropic compounds may be estimated using a cell based mathematical model.[7]
A significant part of the clinically approved drugs are lipophilic weak bases with lysosomotropic properties. This explaines a number of pharmacological properties of these drugs, such as high tissue-to-blood concentration gradients or long tissue elimination half-lifes; these properties have been found for drugs such as haloperidol,[8] levomepromazine [9] and amantadine.[10] However, in addition to lysosomotropism, high tissue concentrations and long elimination half-life is explained also by lipophilicity and absorption of drugs to fatty tissue structures. Important lysosomal enzymes, such as acid sphingomyelinase, may be inhibited by lysososomally accumulated drugs.[11][12] Such compounds are termed FIASMAs (functional inhibitor of acid sphingomyelinase)[13]and include for example fluoxetine, sertraline or amitriptyline.
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